A call to retract the JNC-8 hypertension guidelines

JAMA published the long-awaited Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure-8 (JNC-8) guidelines December 18, 2013. They recommended blood pressure lowering drug treatment for patients ≥ 60-years-old with systolic blood pressure (SBP) ≥ 150 or diastolic blood pressure (DBP) ≥ 90 mm Hg. For patients < 60-years-old, they recommended medications for DBP ≥ 90 mm Hg. They classified both of these recommendations as “Grade A” (strong). To say the least, the evidence-basis for the drug treatment recommendations for mild hypertension in this report is in dispute.

The JNC-8 authors simply ignored a systematic review that I co-authored in the Cochrane Database of Systematic Reviews that found no evidence supporting drug treatment for patients of any age with mild hypertension (SBP: 140-159 and/or DBP 90-99) and no previous cardiovascular disease, diabetes, or renal disease (i.e., low risk).

The JNC-8 hypertension guidelines are not endorsed by the National Heart, Lung, and Blood Institute (NHLBI), the American Heart Association, the American College of Cardiology, nor any other authoritative body. They are endorsed only by the 17 JNC-8 panelists and various individuals such as Dr. Howard Bauchner, editor-in-chief of JAMA and two colleagues from the journal’s editorial staff who authored an editorial accompanying the new BP guidelines. The editorial mentioned that the guidelines, “appropriately acknowledged the areas of controversy.” However, there was no mention in the guidelines about controversy concerning the BP threshold of initiating drug treatment in low risk people.

Notably, the JAMA systematic review editor invited my Cochrane review colleagues and me last spring to submit a synopsis of our systematic review of drug treatment for mild hypertension. In the summer, after several drafts of the synopsis were circulated to and from the editor, she withdrew the offer stating, “the studies we reviewed were old and that they didn’t think these studies were sufficient to address whether drugs worked or not.”

JNC-8 report matter-of-factly acknowledged 2 limitations, but did not elaborate on the implications of those huge flaws that go to the essence of what is meant by “evidence-based”:

“The evidence review did not include observational studies, systematic reviews, or meta-analyses, and the panel did not conduct its own meta-analysis based on prespecified inclusion criteria. Thus, information from these types of studies was not incorporated into the evidence statements or recommendations.”

“Although adverse effects and harms of antihypertensive treatment documented in the randomized controlled trials (RCTs) were considered when the panel made its decisions, the review was not designed to determine whether therapy-associated adverse effects and harms resulted in significant changes in important health outcomes.”

In effect, these limitations mean that the JNC-8 guidelines were not based on a systematic review of the data, and there was not a thorough analysis of the adverse effect and harms of drugs used for hypertension.

The division of the JNC-8 drug treatment recommendations according to age (≥ 60 years old versus < 60 years old) is new compared with previous JNC guidelines (JNC-1 – JNC-7). It is completely unsupported by RCT evidence. For patients ≥ 60 years-old, the JNC-8 panel raised the threshold for drug treatment from 140/90 mm Hg to 150/90 mm Hg. In relation to this changed drug treatment threshold recommendation, the JNC-8 panel cited 6 RCTs. The first 3 of these placebo controlled RCTs (Staessen, Beckett, and SHEP) involve only patients with stage 2 hypertension (SBP ≥ 160) rather than mild (stage 1) hypertension. RCTs of stage 2 patients say nothing about the important issue, which is whether the threshold to begin drug treatment should be at SBP = 140, 150, or 160. The widely acknowledged benefits of drugs for stage 2 hypertension were inappropriately extrapolated to apply to patients with stage 1 hypertension. The last 3 RCTs (Jatos, Ogihara, and Verdecchia) involved almost exclusively stage 2 hypertension patients and had no placebo control arms. These studies tell us nothing about the efficacy and safety of drugs for mild hypertension.

The JNC-8 authors referenced 5 RCTs as providing “high quality evidence” to support their strong (Grade A) recommendation for drug use above a threshold of DBP ≥ 90:

The hypertension detection and follow up program (HDFP) was excluded from our Cochrane review of drugs for mild hypertension because it did not have a placebo or no treatment arm in the trial and it mixed stage 1 and 2 patients.

The U.K. Medical Research Council Working Party trial (DBP 90-109) mixed the results of stage 1 and 2 patients. For our Cochrane review of drugs for mild hypertension, we included about 40% of the patients in this study because we could obtain individual subject data on treatment and outcomes. We found no significant benefit in stroke, health attacks of other cardiovascular disease outcomes.

The Hypertension-Stroke Cooperative Study Group study found no benefit from blood pressure lowering drugs in patients after a stroke.

As I noted in a guest post for Health News Review titled, “The Economics & Politics of Drugs for Mild Hypertension,” there is no evidence that drugs benefit tens of millions of low risk Americans with mild hypertension. About 2 million low cardiovascular disease risk Americans with stage 1 hypertension (about 9% of those taking drugs) suffer side effects from blood pressure lowering drugs severe enough for them to stop treatment. The cost for drugs and clinic visits to comply with these JNC-8 guidelines over the next 10 years is projected from American Heart Association data to be almost $500 billion.

I call for JAMA to retract the JNC-8 guidelines, because they are demonstrably not evidence-based and are likely to harm patients medically and financially.

A call to retract the JNC-8 hypertension guidelines 5 comments

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godsfshrmn

It was funded by NHLBI

David K Cundiff

In support of drugs for > 150/90 mm/Hg in people ≥ 60 years old, 5/6 of the RCTs cited by the JNC-8 panel were drug company funded. All 5 of the old RCTs used
to support drugs for stage 1 patients < 60 years old were funded by governments. Four of the 17 JNC-8 panelists reported extensive financial relationships with drug companies. The NHLBI funded the JNC-8 and the previous JNC guidelines. Hypertension experts from 5 NHLBI agencies and 16 other NHLBI hypertension experts gave input to the JNC-8 panel. Consequently, the NHLBI must have endorsed the drug treatment of people with mild hypertension. Three weeks after the publication of the Cochrane review of drugs for mild hypertension, the Center for Disease Control published “Vital Signs: Awareness and Treatment of Uncontrolled Hypertension Among Adults — United States, 2003–2010,” a call to action for physicians to increase the number of hypertensive people on “treatment”, meaning drug treatment.1 The lead author, Dr. Amy Valderrama told me that the CDC was aware that our
Cochrane review findings did not support drugs for mild hypertension but that they awaited the JNC-8 findings regarding any policy changes. Nowhere has any
representative of the NHLBI or the JNC-8 panel acknowledged that any controversy exists about the drugs for mild hypertension mandate in the guidelines.

Apparently there are so many conflicts of interest and financial relationships with industry, it’s really hard to be sure of anything IMHO.

David K Cundiff

As you know, the non drug approaches for management
of hypertension and the associated cardiovascular disease risks include diet, exercise, relaxation therapies, smoking cessation, and alcohol moderation. The DASH diet
(“Dietary Approaches to Stop Hypertension”) reduced mean systolic blood pressure by 11.5 mmHg in participants with hypertension as compared to a control diet. The Mediterranean
Diet has been shown to reduce total mortality by 56% and adverse cardiovascular events by 47% in patients at high cardiovascular disease risk. The intensive lifestyle change program of Dr. Dean Ornish for cardiovascular disease patients reduced cardiovascular events in half in 5 years. None of the RCTs, on which the JNC-8 based its drugs for mild hypertension, included aggressive approaches to lifestyle change for reducing cardiovascular disease risk. The DASH diet has been considered the standard of care for people with hypertension since the original article was published in the New England Journal of Medicine in 1997 and referenced later that year in the JNC-6 hypertension guidelines. The DASH diet and regular aerobic physical activity such as brisk walking (at
least 30 min per day, most days of the week) were recommended in the JNC-7 hypertension guidelines published in 2003. However, none of the drug company funded RCTs published after 2003 and referenced by JNC-8 in support of
drugs for mild hypertension (Beckett, Jatos, Ogihara, and Verdecchia) included the DASH diet intervention or exercise for both arms of these trials. Unfortunately, drug company funded trials have a major disincentive to include state of the art lifestyle change interventions. In RCTs, if diet, exercise and other therapeutic lifestyle change interventions are highly successful, drugs will then be less effective in comparison. The authors of any future drug treatment trials for hypertension should assure that all patients are receiving at least the standard of care lifestyle change interventions. Even better would be that all future hypertension trials include methodologies that test the efficacy of ever more aggressive lifestyle change interventions.

David K Cundiff

Thank you for your observation, Dr. Tom. It’s not just the
patients wanting pills, the entire health care industrial complex is strongly weighted toward medicines and away from diet and lifestyle change. Unless you are lucky enough to be affiliated with an excellent health promotion program for you to refer patients, your five minutes of lifestyle modification advice
to clinic patients is unlikely to be fruitful. Since medications and other sickness care interventions consume most of the resources for health care, little is left for wellness programs. The media may give lip service to lifestyle interventions but gives most attention to drugs and high tech interventions.
The JNC-8 panelists have yet to rebut the case that drugs are ineffective for stage 1 hypertension and do patients medical and financial harm. No medical journalist has asked the JNC-8 panelists to respond to my call for retracting the drugs for stage 1 hypertension guidelines and reported the story. However, several medical journalists have published stories about the editorial of JNC-8 dissenting panelists that want to retain the threshold for drug treatment of patients ≥ 60 years-old at 140/90. None has asked the JNC-8 panelists to
comment on the Cochrane review of drugs for mild hypertension that found no proven benefit of drugs for stage 1 hypertension.

Well Dr. Tom, welcome to evidence based medicine. Keep up
the struggle to motivate patients to adopt healthy lifestyles.